Favipiravir, an anti-influenza drug against life-threatening RNA virus infections

Shiraki, Kimíyasu; Daikoku, Tohru

doi:10.1016/j.pharmthera.2020.107512

Cited by 401 publications

(346 citation statements)

References 120 publications

Supporting

Mentioning

333

Contrasting

Unclassified

Order By: Relevance

“…The half-life is approximately 5 hours. 70 The agent has a mild adverse effect profile and is overall well-tolerated, although the adverse event profile for higher-dose regimens is limited. 44,69,71,72 Favipiravir is currently available in Japan for the treatment of influenza, but not available in the United States for clinical use.…”

Section: Review Of Select Investigational Drugsmentioning

confidence: 99%

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19)

Sanders

Monogue

Jodlowski

et al. 2020

JAMA

2,281

2,770

View full text Add to dashboard Cite

he global pandemic of novel coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019, and has since spread worldwide. 1 As of April 5, 2020, there have been more than 1.2 million reported cases and 69 000 deaths in more than 200 countries. This novel Betacoronavirus is similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV); based on its genetic proximity, it likely originated from bat-derived coronaviruses with spread via an unknown intermediate mammal host to humans. 1 The viral genome of SARS-CoV-2 was rapidly sequenced to enable diagnostic testing, epidemiologic tracking, and development of preventive and therapeutic strategies.Currently, there is no evidence from randomized clinical trials (RCTs) that any potential therapy improves outcomes in patients with either suspected or confirmed COVID-19. There are no clinical trial data supporting any prophylactic therapy. More than 300 active clinical treatment trials are underway. This narrative review summarizes current evidence regarding major proposed treatments, repurposed or experimental, for COVID-19 and provides a summary of current clinical experience and treatment guidance for this novel epidemic coronavirus. MethodsA literature review was performed using PubMed to identify relevant English-language articles published through March 25, 2020. Search terms included coronavirus, severe acute respiratory syndrome coronavirus 2, 2019-nCoV, SARS-CoV-2, SARS-CoV, MERS-CoV, and COVID-19 in combination with treatment and pharmacology. The search resulted in 1315 total articles. Due to the lack of RCTs, the authors also included case reports, case series, and review articles. The authors independently reviewed the titles and abstracts for inclusion. Additional relevant articles were identified from the review of citations referenced. Active clinical trials were identified using the disease search term coronavirus infection on ClinicalTrials.gov and the index of studies of novel coronavirus pneumonia in the Chinese Clinical Trial Registry. 2 SARS-CoV-2: Virology and Drug Targets SARS-CoV-2, a single-stranded RNA-enveloped virus, targets cells through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Following IMPORTANCE The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.OBSERVATIONS No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The mo...

show abstract

Section: Review Of Select Investigational Drugsmentioning

confidence: 99%

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19)

Sanders

Monogue

Jodlowski

et al. 2020

JAMA

2,281

2,770

View full text Add to dashboard Cite

show abstract

“…Favipiravir has been developed as an anti-influenza drug and is licensed as an anti-influenza drug in Japan [5]. One of the unique features of favipiravir is its broad-spectrum activity against RNA viruses, including influenza virus, rhinovirus and respiratory syncytial virus.…”

Section: Favipiravir (Avigan T-705)mentioning

confidence: 99%

“…One of the unique features of favipiravir is its broad-spectrum activity against RNA viruses, including influenza virus, rhinovirus and respiratory syncytial virus. Previous studies demonstrated that favipiravir is effective at treating infections with Ebola virus, Lassa virus and rabies, and against severe fever with thrombocytopenia syndrome [5]. However, favipiravir is not effective against DNA viruses.…”

Section: Favipiravir (Avigan T-705)mentioning

confidence: 99%

“…With regard to its mechanism, it is reported that favipiravir antagonizes viral RNA synthesis by acting as a chain terminator at the site where the RNA is incorporated into the host cell. By contrast, oseltamivir (Tamiflu), a neuraminidase inhibitor, blocks the cleavage of sialic acid and the subsequent entry of the virus into the cell [5]. Importantly, favipiravir, unlike oseltamivir, does not seem to generate resistant viruses [5].…”

Section: Favipiravir (Avigan T-705)mentioning

confidence: 99%

See 1 more Smart Citation

COVID-19 Drug Discovery Using Intensive Approaches

Asai

Konno

Ozaki

et al. 2020

IJMS

View full text Add to dashboard Cite

Since the infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China during December 2019, the coronavirus disease 2019 has spread on a global scale, causing the World Health Organization (WHO) to issue a warning. While novel vaccines and drugs that target SARS-CoV-2 are under development, this review provides information on therapeutics which are under clinical trials or are proposed to antagonize SARS-CoV-2. Based on the information gained from the responses to other RNA coronaviruses, including the strains that cause severe acute respiratory syndrome (SARS)-coronaviruses and Middle East respiratory syndrome (MERS), drug repurposing might be a viable strategy. Since several antiviral therapies can inhibit viral replication cycles or relieve symptoms, mechanisms unique to RNA viruses will be important for the clinical development of antivirals against SARS-CoV-2. Given that several currently marketed drugs may be efficient therapeutic agents for severe COVID-19 cases, they may be beneficial for future viral pandemics and other infections caused by RNA viruses when standard treatments are unavailable.

show abstract

“…Among the main actors of SARS-CoV-2 infection the SARS-CoV-2 spike proteins, RNA dependent RNA polymerases and proteases deserve to be mentioned. Indeed, RNA dependent RNA polymerase has become one of the main targets of a nucleoside analog antiviral drug, the remdesivir, already used for reducing complications due to Ebola, Dengue and MERS-CoV infections (1)(2)(3)(4)(5)(6). At the same time viral protease inhibitors (7)(8)(9)(10) are under investigation for their ability in preventing virus protein (with specific reference to spike proteins) cleavage (11) leading to the fusion of virus proteins with host cell membranes.…”

Section: Introductionmentioning

confidence: 99%

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies

Mercurio

Tragni

Busco

et al. 2020

Preprint

View full text Add to dashboard Cite

Abbreviations: Severe acute respiratory syndrome, SARS; coronavirus CoV; receptor binding domain, RBD; angiotensin converting enzyme 2, ACE2; fragment antigen binding, FAB; Word Health Organizzation, WHO; complementary-determining regions, (CDR); SwissPDBViewer, SPDBV. ABSTRACT The recent severe acute respiratory syndrome, known as Corona Virus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim we performed an in silico comparative modeling analysis, which allows to gain new insights about the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor binding domain (RBD), along interactions with human cells angiotensin converting enzyme 2 (ACE2) receptor, that favour human cell invasion. Furthermore, our analysis provides i) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, for preventing interactions with the human ACE2, and ii) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico a high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high affinity antibodies against present and future coronavirus able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnosis kits and other treatments based on the usage or the targeting of SARS-CoV-2 spike protein.

show abstract

Favipiravir, an anti-influenza drug against life-threatening RNA virus infections

Cited by 401 publications

References 120 publications

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19)

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19)

COVID-19 Drug Discovery Using Intensive Approaches

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies

Contact Info

Product

Resources

About